CHROMOSOME STABILITY

Coordination of DNA replication and DNA repair at single-forks: the role of the Smc5-Smc6 complex in replication fork stalling and resumption

 Coordinatore IMPERIAL COLLEGE OF SCIENCE, TECHNOLOGY AND MEDICINE 

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 Nazionalità Coordinatore United Kingdom [UK]
 Totale costo 893˙396 €
 EC contributo 893˙396 €
 Programma FP7-IDEAS-ERC
Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
 Code Call ERC-2007-StG
 Funding Scheme ERC-SG
 Anno di inizio 2008
 Periodo (anno-mese-giorno) 2008-09-01   -   2013-08-31

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    IMPERIAL COLLEGE OF SCIENCE, TECHNOLOGY AND MEDICINE

 Organization address address: SOUTH KENSINGTON CAMPUS EXHIBITION ROAD
city: LONDON
postcode: SW7 2AZ

contact info
Titolo: Dr.
Nome: Luis Fernando
Cognome: Aragon Alcaide
Email: send email
Telefono: -83833684
Fax: -83838282

UK (LONDON) hostInstitution 0.00
2    IMPERIAL COLLEGE OF SCIENCE, TECHNOLOGY AND MEDICINE

 Organization address address: SOUTH KENSINGTON CAMPUS EXHIBITION ROAD
city: LONDON
postcode: SW7 2AZ

contact info
Titolo: Ms.
Nome: Tatjana
Cognome: Palalic
Email: send email
Telefono: +44 20 8383 2241
Fax: +44 20 8383 2207

UK (LONDON) hostInstitution 0.00

Mappa


 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

roles    function    fork    replication    mechanisms    single    nse    recombination    techniques    substrates    repair    integrity    assays    stability    forks    restart    progression    addition    collapse    dna    smc    stalled   

 Obiettivo del progetto (Objective)

'DNA replication represents a dangerous moment in the life of the cell as endogenous and exogenous events challenge genome integrity by interfering with the progression, stability and restart of the replication fork. Failure to protect stalled forks or to process the replication fork appropriately contribute to the pathological mechanisms giving rise to cancer, therefore an understanding of the intricate mechanisms that ensure fork integrity can provide targets for new chemotherapeutic assays. Smc5-Smc6 is a multi-subunit complex with a poorly understood function in DNA replication and repair. One of its subunits, Nse2, is able to promote the addition of a small ubiquitin-like protein modifier (SUMO) to specific target proteins. Recent work has revealed that the Smc5-Smc6 complex is required for the progression of replication forks through damaged DNA and is recruited de novo to forks that undergo collapse. In addition, Smc5-Smc6 mediate repair of DNA breaks by homologous recombination between sister-chromatids. Thus, Smc5-Smc6 is anticipated to promote recombinational repair at stalled/collapsed replication forks. My laboratory proposes to develop molecular techniques to study replication at the level of single replication forks. We will employ these assays to identify and dissect the function of factors involved in replication fork stability and repair. We will place an emphasis on the study of the Smc5-Smc6 complex in these processes because of its potential roles in recombination-dependent fork repair and restart. We also propose to identify novel Nse2 substrates involved in DNA repair using yeast model systems. Specifically, we will address the following points: (1) Development of assays for analysis of factors involved in stabilisation, collapse and re-start of single-forks, (2) Analysis of the roles of Smc5-Smc6 in fork biology using developed techniques, (3) Isolation and functional analysis of novel Nse2 substrates.'

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